219 Correlation between clinical chorionicity and SNP-based cfDNA zygosity assignment in 38,808 twin pregnancies

Abstract

Chorionicity is the most significant risk factor for adverse outcomes in twin pregnancies and relies on ultrasound (US) assessment. Many factors impact the accuracy of US, including gestational age and operator experience. SNP-based cfDNA testing for zygosity in twins is now possible (pb226). We hypothesize that discordance may be found between provider-supplied chorionicity and SNP-based cfDNA assignment of zygosity. This updated cohort analysis examined twin pregnancy samples received between September 27, 2017 and July 24, 2020. Egg-donor or surrogate pregnancies, and samples that failed quality check were excluded. Demographic information included information on chorionicity assignment prior to blood draw (monochorionic (MC), dichorionic (DC), undetermined, or left blank). Zygosity result from cfDNA was correlated with chorionicity assignment. A total of 38,808 twin samples were received and analyzed, of which 37,172 received zygosity assignment. The mean gestational age at blood draw was 13.1 weeks (range 9.0-36.0). cfDNA reported 10,813/37,172 (29.1%) as monozygotic (MZ) and 26,359/37,172 (70.9%) as dizygotic (DZ). Table 1 represents provider reported chorionicity information and the corresponding zygosity assignment. Of 4,179 suspected MC twins, 216 (5.2%) were reported as DZ using cfDNA. A total of 1,636 samples (4.2%) did not receive a result for zygosity, of which 2.5% were eligible for redraw (predominantly due to low fetal fraction). The remaining 1.7% had algorithm limitations that were unlikely to resolve with repeat sampling. Almost 30% of 37,172 twin pregnancies were found to be MZ, even in cases where chorionicity is unknown. 1 in 20 suspected MC twin pregnancies were adjusted as DZ using SNP-based cfDNA. Further US assessment may clarify the utility of surveillance for twin-twin transfusion syndrome and other MC-related pregnancy complications. In cases with undetermined or uncertain chorionicity, early knowledge of zygosity can be factored into US evaluation and proper counseling can be provided.